Mast cell deficiency induces inflammation and exacerbates inflammatory bowel symptoms in IL10−/− mice

Abstract

BackgroundThe interleukin 10 deficient (IL10−/−) mice has abnormal intestinal immune responses against enteric antigens, leading to sustained inflammation, and develops inflammatory bowel disease spontaneously. Mast cells abundantly present under gut epithelium and are critical for gut immune response. The objective is to test the role of mast cells in gut inflammation and barrier function using IL10−/− mice.MethodsMast cell deficient (KitW‐sh/W‐sh) mice were crossbred with IL10−/− mice to obtain double knockout (DKO) mice. Mucosal damage and colitis status were compared between DKO and their IL10−/− littermates.ResultsMast cell deficiency enhanced gut mucosal damage and colitis as revealed by increased gut permeability and impaired tight junction protein expression, increased pathobiological score, higher myeloperoxidase content and pronounced goblet cell loss in DKO mice. In addition, DKO mice showed splenomegaly and elevated serum TNFα and INF levels, indicating exaggerated systemic inflammation. Consistently, the colon of DKO mice demonstrated enhanced inflammation and oxidative stress.ConclusionsMast cell deficiency induced systemic inflammation, and inflammation and oxidative stress in the colon, which might explain the impaired gut barrier function and severe colitis in DKO mice. NIH 1R15HD073864; INBRE P20RR016474; USDA 2008–35203‐19084; 2009–65203‐05716